Breast and Female reproductive system Flashcards
Breast pathology
Terminal duct lobular units are the site of origin of most proliferative breast disease, including cancers and precursor lesions.
The epithelium of the terminal ducts rather than the acini is considered more prone to neoplastic transformation and more susceptible to environmental factors which initiate malignant change.
Lobules are embedded in a loose specialized connective tissue stroma which is itself altered in certain disease states.
Aberrations of normal development and involution (ANDI)
The following pathological entities are included within this umbrella term.
- Fibrosis
- Cyst formation
- Adenosis
- Sclerosing adenosis
- Epithelial hyperplasia
Aberrations of normal development and involution (ANDI): Fibrosis
The following pathological entities are included within this umbrella term.
• Fibrosis – an increase in collagen rather than an overgrowth of fibrous tissue
Aberrations of normal development and involution (ANDI): Cyst formation
• Cyst formation – cysts are more common in women approaching the menopause and represent involutional changes. Lobular units unfold and coalesce with loss of specialized connective tissue. This creates a walled space filled with fluid which can vary in size from a few millimeters (microcyst) to several centimeters (macrocyst). Lining epithelial cells tend to be large with abundant granular eosinophilic cytoplasm and basal nuclei (apocrine metaplasia). Diagnosis is confirmed by aspiration and cytology is indicated only if the aspirate is blood-stained (intracystic papilloma
or carcinoma) or the cyst refills. Cysts constitute up to 15% of all discrete breast lumps and do not predispose to cancer;
Aberrations of normal development and involution (ANDI): Adenosis
• Adenosis – an increase in the number of acini or ductules within a lobule without thickening of the ductular epithelium. It is usually of the blunt duct type in which alveoli showed marked dilatation and an irregular outline
Aberrations of normal development and involution (ANDI): Sclerosing adenosis
• Sclerosing adenosis – this is an abnormality
of stromal involution leading to localized proliferation of both stroma and acini. There is prominent mitotic activity but no dysplasia and the lobules are distorted with infiltrative margins. These lesions often form a mass macroscopically containing microcalcification. They can be clinically, radiologically and pathologically indeterminate and mimic cancer;
Aberrations of normal development and involution (ANDI): epithelial hyperplasia
• Epithelial hyperplasia – this is a benign proliferation most commonly affecting the TDLU and the interlobular ducts. Hyperplasia is an increase in the number of cell layers above the basement membrane. Though there is no cytological atypia and the condition is benign, more severe forms (moderate or florid) are associated with increased risk of malignancy (relative risk (RR) 1.5–2.0 times). Ordinary hyperplasia or hyperplasia of the usual type is assumed to be of ductal origin and cannot readily be distinguished from hyperplasia arising in the lobules of the TDLU. In mild forms, spaces are lined by 3–4 cell layers, whilst in moderate to severe forms this exceeds 4 cells in thickness and there may be proliferating cell masses distending and distorting involved spaces.
Atypical hyperplasia
Atypical hyperplasia refers to lesions with both an overgrowth of epithelium and cytological atypia. These are found in approximately 4% of benign breast biopsies from the pre-mammographic era and increase risk of breast cancer (4–5 times RR).
lobular carcinoma-in-situ (LCIS)
A specific pattern of atypical lobular hyperplasia is recognized which is often associated with lobular carcinoma-in-situ (LCIS).
Both atypical hyperplasia and LCIS distend the acini within a lobular unit to varying extent. Unlike ductal carcinoma-in-situ (DCIS), LCIS is considered
to be a marker of breast cancer risk and not a precursor lesion for invasive malignancy.
There are stringent histopathological criteria for describing atypical hyperplasia which lies on a pathological continuum with in situ carcinoma (CIS).
These include normal polarity of cells around the periphery of the space, but sharply defined secondary spaces and rigid cellular bars resemble CIS (Fig. 15.4).
Fibroadenoma
1) Though often described as a benign tumour these circumscribed breast masses are hyperplastic lesions which are really a localized form of ANDI.
2) They arise from a single lobule rather than a single cell and respond to cyclical hormonal changes within the breast. Most undergo spontaneous regression; small fibroadenomas can be subclinical and discovered incidentally on imaging (commonest cause of a breast lump under 30 years of age).
Duct ectasia
This is an involutional change characterized by dilatation and shortening of the subareolar ducts.
Mild ectasia occurs in almost half of peri-menopausal women and more severe forms can be associated with periductal inflammation and fibrosis.
Fat necrosis
Trauma to the breast can result in localized ischaemia and fat necrosis. Subsequent inflammation and fibro-elastic reactions can produce a hard irregular lump tethered to skin which mimics a carcinoma.
Infection and inflammation of the breast
Inflammation and infection of the breast occurs almost exclusively in adult females, most commonly during lactation.
Periductal inflammation
Periductal inflammation occurs in perimenopausal women and is often sterile, at least initially. This can progress to periareolar sepsis with abscess formation.
Puerperal breast abscesses
Puerperal breast abscesses occur during or soon after lactation and are usually pyogenic with the causative organism being Staphylococcus aureus.
Infection and inflammation
Infection probably is introduced via cracked or traumatized nipples during suckling. Infection commences within the main lactiferous ducts producing local inflammation which progresses to a generalized cellulitis affecting one radial section of the breast.
At this stage, when there is no focal collection of pus, the infection can be successfully treated with intravenous anti-staphylococcal agents.
However, once abscess formation occurs, pus must be surgically drained in order for resolution of the inflammatory process. If surgical intervention is deferred, then the combination of inflammation and scarring can destroy a large part of the breast parenchyma.
It may be possible to successfully drain these abscesses percutaneously under ultrasound control, provided they are not loculated and the contents are relatively pure pus with minimal debris.
More complex abscesses should be drained via an incision placed some distance from the areolar and the wound closed around a corrugated drain which is left in situ for a few days.
Carcinoma-in-situ
Carcinoma-in-situ was first described in 1932 as a neoplastic condition in which malignant epithelial cell proliferation was confined within the ducts and acini of the TDLU with no migration across the basement membrane.
There is an ‘unfolding’ of the lobules with incorporation into a single lumen. As the process involves mainly the ductules of the lobules, the term ductal carcinoma is used, but this refers to a histological pattern and not tissue of origin. LCIS has a readily recognized ‘pure’ form with characteristic histological appearances.
Ductal carcinoma in situ
This is a complex disease entity with several histo- logical variants, including comedo, cribriform, solid and micropapillary. These architectural forms do not predict behaviour and from a clinical and prognostic point of view, DCIS is categorized as high, intermediate and low nuclear grade.
Up to 85% of high grade lesions show comedo necrosis, so called because of the gross appearance of caseous material dotting the cut surface and resembling a ‘comedone’. This corresponds to necrotic debris within the ductule lumen. Dystrophic deposits of calcium produce coarse linear branching calcification on mammography. Neoplastic cells lining the ducts are usually arranged as solid sheets with central necrosis.
Non-high grade DCIS
Non-high grade DCIS (low and intermediate grade) can be associated with necrosis but more often are not, and consist of several architectural patterns including cribriform, micro- papillary as well as solid types.
There is a close association between nuclear grade and necrosis; high nuclear grade lesions with necrosis are more likely to exhibit obligate progression to invasive disease and to have foci of micro-invasion. They are more likely to recur after conservation surgery and for this reason all cases of high grade DCIS managed with wide local excision now receive radiotherapy to the breast.
Lobular carcinoma in situ
This has a rather monotonous histological appearance with uniform cells distending more than half the acini within a lobular unit (Fig. 15.5).
It is a silent process with the diagnosis made incidentally on biopsies performed for other conditions. LCIS is present in approximately 1% of screen-detected lesions, and tends to occur as multi-centric and bilateral lesions in pre-menopausal women.
The condition is not a direct precursor lesion but a marker of risk (10–11 times RR) for development of invasive cancer. Indeed, the con- dition may regress after the menopause. The absolute risk for invasive malignancy is 25–30% at 15–20 years.
